The antihemophilic factor (Factor VIII) is a high-molecular-weight glycoprotein which functions as a regulatory protein in the intrinsic mechanism of blood coagulation and is also involved in platelet aggregation. The high carbohydrate content (20%) of Factor VIII suggests that the carbohydrate may play a significant role in the structure and function of the Factor VIII. This project is a study of bovine Factor VIII molecule, especially the carbohydrate portion of the Factor VIII, and of the physiological function of the carbohydrate on the Factor VIII. The Factor VIII molecule will be cleaved into smaller fragments with plasmin, the individual fragments purified, and the molecular weight, composition, physiological activity, and immunological activity of each fragment determined. Investigations will also be made on the carbohydrate composition and structure on each of the individual fragments and the intact Factor VIII molecule. The role of the carbohydrate on Factor VIII will be investigated by sequentially cleaving off certain of the sugar moieties with specific glycosidases and comparing the treated Factor VIII to native Factor VIII in terms of its structure and its procoagulant, platelet-agglutinating, and immunological activities. These studies should provide a greater understanding not only of the basic structure of Factor VIII, but also of the molecular basis for its physiological and immunological activities. These findings could be important not only in the treatment of hemophilia, but also for the management of certain hypercoagulable states.